Neuronal, glial, and epithelial localization of ?-aminobutyric acid transporter 2, a high-affinity ?-aminobutyric acid plasma membrane transporter, in the cerebral cortex and neighboring structures

Conti, Fiorenzo; Zuccarello, Laura Vitellaro; Barbaresi, Paolo; Minelli, Andrea; Brecha, Nicholas C.; Melone, Marcello

doi:10.1002/(sici)1096-9861(19990705)409:3<482::aid-cne11>3.0.co;2-o

Cited by 96 publications

(63 citation statements)

References 66 publications

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“…While binding studies have localized GAT-1, GAT-2, and GAT-3 expression to astrocytic processes within the cortex (Conti et al 1998Minelli et al 1995), this study strongly suggests that functional, co-localized GAT transporters are expressed on these cells. While the presence of the GAT-1 transporter can be confirmed from the use of NO-711/SKF89976a, the identity of the ␤-alanine-sensitive current cannot be established because both GAT-2 and GAT-3 transporters are blocked by ␤-alanine at higher doses (Borden et al 1995b) and the expression of both transporter subtypes on neocortical astrocytes has been confirmed Minelli et al 1996;Yan and Ribak 1999).…”

Section: Transporter Expressionmentioning

confidence: 56%

“…Of course, glial GABA transporters may have other important functions as well, such as to supply a source of extracellular GABA via reversal of the GABA transporter (Wu et al 2001) and to regulate paracrine GABA, as has been suggested by others (Conti et al 1998;Minelli et al 1996). The relatively distal localization of glial GABA transporters, as compared with glutamate transporters, suggested by the long transporter current time course is consistent with this hypothesis.…”

Section: Functional Considerationsmentioning

confidence: 97%

“…The origin of this portion of the current is unknown. Antagonism of the GAT transporters may be incomplete or other subtypes of GABA transporters may be present on the astrocytes that are insensitive to the antagonists used (e.g., Borden et al 1995a;Conti et al 1999). Alternatively, there is the possibility that other neurotransmitter or peptide transporters are present on the astrocytes, which are activated during synaptic stimulation.…”

Section: Transporter Expressionmentioning

confidence: 99%

“…GAT-1 expression within the cortex has been shown to be high and is localized to puncta and fibers and astrocytic processes as well as a few pyramidal cells; its expression has been shown to have a high correlation with the soma and proximal dendrites of unlabeled pyramidal cells, indicative of localization at inhibitory synapses (Conti et al 1998;DeFelipe and González-Albo 1998;Durkin et al 1995;Minelli et al 1995). GAT-3 has been shown to be expressed primarily in glia (Clark et al 1992;Durkin et al 1995;Minelli et al 1996;Yan and Ribak 1999); its expression in the cortex has been shown to be low in the adult (Minelli et al 1996;Yan and Ribak 1999) and may be developmentally regulated (Jursky and Nelson 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it is not known whether the GABA transporter actively removes GABA during a synaptic event or serves as a buffer as has been suggested for the glutamate transporter (Diamond and Jahr 1997;Tong and Jahr 1994; but see Mennerick et al 1999). In the cortex, glial uptake of GABA may serve to primarily regulate paracrine levels of GABA rather than participate in uptake of GABA during a synaptic event (Conti et al 1998;Ribak et al 1996;Spreafico et al 1993), although there is some evidence that glial GABA transporters in the cortex (Minelli et al 1996) and elsewhere in the brain (De Biasi et al 1998) are located at sites very close to release.…”

Section: Introductionmentioning

confidence: 99%

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Synaptically Evoked GABA Transporter Currents in Neocortical Glia

Kinney

Spain

2002

Journal of Neurophysiology

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. The presence, magnitude, and time course of GABA transporter currents were investigated in electrophysiologically characterized neocortical astrocytes in an in vitro slice preparation. On stimulation with a bipolar-tungsten stimulating electrode placed nearby, the majority of cells tested displayed long-lasting GABA transporter currents using both single and repetitive stimulation protocols. Using subtype-specific GABA transporter antagonists, long-lasting GABA transporter currents were identified in neocortical astrocytes that originated from at least two subtypes of GABA transporters: GAT-1 and GAT-2/3. These transporter currents displayed slow rise times and long decay times, contrasting the time course observed for glutamate transporter currents, and are indicative of a long extracellular time course of GABA as well as a role for glial GABA transporters during synaptic transmission.

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Section: Transporter Expressionmentioning

confidence: 56%

Section: Functional Considerationsmentioning

confidence: 97%

Section: Transporter Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synaptically Evoked GABA Transporter Currents in Neocortical Glia

Kinney

Spain

2002

Journal of Neurophysiology

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?-aminobutyric acid transporters in the cat periaqueductal gray: A light and electron microscopic immunocytochemical study

2000

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The gamma-aminobutyric acid (GABA) plasma membrane transporters (GATs) mediate GABA uptake into presynaptic axon terminals and glial processes, thus contributing to the regulation of the magnitude and duration of the action of GABA at the synaptic cleft. The aim of the present study was to investigate the expression of three high-affinity GABA transporters (GAT-1, GAT-2, and GAT-3) in the periaqueductal gray matter (PAG) of adult cats by using immunocytochemistry with affinity-purified antibodies. Light microscopic observations revealed GAT-1 immunoreactivity in punctate structures, particularly dense in the lateral portion of the dorsolateral PAG column. Weak GAT-2-immunopositive puncta were homogeneously distributed in the PAG. GAT-3 immunoreactivity was detected in each column of the PAG but was more intense in the dorsolateral PAG column and around the aqueduct. Electron microscopic studies showed GAT-1 immunoreactivity in distal astroglial processes, in unmyelinated and small myelinated axons, and in axon terminals making symmetric synapses on both PAG neurons and dendrites. GAT-2 immunoreactivity was present mostly in the form of patches of different sizes in the cytoplasm of neuronal elements like the perikarya and dendrites of PAG neurons, in myelinated and unmyelinated axons, and in the axon terminals forming both symmetric and asymmetric synapses. Labeling was also observed in nonneuronal elements. Astrocytic cell bodies and their distal processes as well as the ependymal cells lining the wall of the aqueduct showed patches of GAT-2 immunoreactivity. Electron microscopic observation revealed GAT-3 immunoreactivity exclusively in distal astrocytic processes adjacent to the somata of PAG neurons and in axon terminals making both symmetric and asymmetric synapses. The present results suggest that three types of termination systems of GABAergic transmission are present in the cat periaqueductal gray matter.

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Subcellular localization of GABAB receptor subunits in rat visual cortex

et al. 2001

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Although studies in the visual cortex have found gamma-aminobutyric acid B (GABA(B)) receptor-mediated pre- and postsynaptic inhibitory effects on neurons, the subcellular localization of GABA(B) receptors in different types of cortical neurons and synapses has not been shown directly. To provide this information, we have used antibodies against the GABA(B) receptor (R)1a/b and GABA(B)R2 subunits and have studied the localization of immunoreactivities in rat visual cortex. Light microscopic analyses have shown that both subunits are expressed in cell bodies and dendrites of 65-92% of corticocortically projecting pyramidal neurons and in 92-100% of parvalbumin (PV)-, calretinin (CR)-, and somatostatin (SOM)-containing GABAergic neurons. Electron microscopic analyses of immunoperoxidase- and immunogold-labeled tissue revealed staining in the nucleus, cytoplasm and cell surface membranes with both antibodies. Colocalization of both subunits was observed in all of these structures. GABA(B)R1a/b and GABA(B)R2 were concentrated in excitatory and inhibitory synapses and in extrasynaptic membranes. In GABAergic synapses, GABA(B)R1a/b and GABA(B)R2 were more strongly expressed postsynaptically on pyramidal and nonpyramidal cells than presynaptically. In type 1 synapses GABA(B)R1a/b and GABA(B)R2 was found in pre- and postsynaptic membranes. The nuclear localization of GABA(B)R1 and GABA(B)R2 subunits suggests a novel role for neurotransmitter receptors in controlling gene expression. The synaptic colocalization of GABA(B)R1 and GABA(B)R2 indicates that subunits form heteromeric assemblies of the functional receptor in inhibitory and excitatory synapses. Subunit coexpression in GABAergic synapses that include PV-containing and PV-deficient terminals suggests that pre- and postsynaptic GABA(B) receptor activation is provided by several different types of interneurons. The coexpression of both subunits in excitatory synapses suggests a role for GABA(B) receptors in the regulation of glutamate release and raises the question how these receptors are activated in the absence of pre-or postsynaptic GABAergic synaptic inputs to excitatory synapses.

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Neuronal, glial, and epithelial localization of ?-aminobutyric acid transporter 2, a high-affinity ?-aminobutyric acid plasma membrane transporter, in the cerebral cortex and neighboring structures

Cited by 96 publications

References 66 publications

Synaptically Evoked GABA Transporter Currents in Neocortical Glia

Synaptically Evoked GABA Transporter Currents in Neocortical Glia

?-aminobutyric acid transporters in the cat periaqueductal gray: A light and electron microscopic immunocytochemical study

Subcellular localization of GABAB receptor subunits in rat visual cortex

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